Synthesis of 5-(4-(1H-phenanthro[9,10-d]imidazol-2-yl)benzylidene)thiazolidine-2,4-dione as promising DNA and serum albumin-binding agents and evaluation of antitumor activity

2019 ◽  
Vol 166 ◽  
pp. 267-280 ◽  
Author(s):  
Iqubal Singh ◽  
Richa Rani ◽  
Vijay Luxami ◽  
Kamaldeep Paul
2018 ◽  
Vol 115 (15) ◽  
pp. E3501-E3508 ◽  
Author(s):  
Junxia Wei ◽  
Tapan K. Bera ◽  
Xiu Fen Liu ◽  
Qi Zhou ◽  
Masanori Onda ◽  
...  

Recombinant immunotoxins (RITs) are chimeric proteins consisting of a Fv that binds to a cancer cell and a portion of a protein toxin. One of these, Moxetumomab pasudotox, was shown to be effective in treating patients with some leukemias, where the cells are readily accessible to the RIT. However, their short half-life limits their efficacy in solid tumors, because penetration into the tumors is slow. Albumin and agents bound to albumin have a long half-life in the circulation. To increase the time tumor cells are exposed to RITs, we have produced and evaluated variants that contain either an albumin-binding domain (ABD) from Streptococcus or single-domain antibodies from Llama. We have inserted these ABDs into RITs targeting mesothelin, between the Fv and the furin cleavage site. We find that these proteins can be produced in large amounts, are very cytotoxic to mesothelin-expressing cancer cell lines, and have a high affinity for human or mouse serum albumin. In mice, the RIT containing an ABD from Streptococcus has a longer half-life and higher antitumor activity than the other two. Its half-life in the circulation of mice ranges from 113 to 194 min compared with 13 min for an RIT with no ABD. Cell uptake studies show the RIT enters the target cell bound to serum albumin. We conclude that RITs with improved half-lives and antitumor activity should be evaluated for the treatment of cancer in humans.


1997 ◽  
Vol 201 (1) ◽  
pp. 115-123 ◽  
Author(s):  
Anders Sjölander ◽  
Per-Åke Nygren ◽  
Stefan Ståhl ◽  
Klavs Berzins ◽  
Mathias Uhlén ◽  
...  

2013 ◽  
Vol 117 (9) ◽  
pp. 2595-2604 ◽  
Author(s):  
Nida Zaidi ◽  
Ejaz Ahmad ◽  
Mohd Rehan ◽  
Gulam Rabbani ◽  
Mohammad R. Ajmal ◽  
...  

1994 ◽  
Vol 33 (6) ◽  
pp. 1239-1243 ◽  
Author(s):  
Swapan K. Nath ◽  
Gary A. Foster ◽  
Lionel A. Mandell ◽  
Coleman Rotstein

2012 ◽  
Vol 153 (3) ◽  
pp. 323-326 ◽  
Author(s):  
G. E. Dobretsov ◽  
T. I. Syrejshchikova ◽  
N. V. Smolina ◽  
and M. G. Uzbekov

Chirality ◽  
2013 ◽  
Vol 25 (4) ◽  
pp. 257-263 ◽  
Author(s):  
Iryna Goncharova ◽  
Sergey Orlov ◽  
Marie Urbanová

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